Open-angle glaucoma (OAG) afflicts 2% of the population over 40 years of age. Its etiology and the factors responsible for its progression are unknown. The ultimate objective of this project is to determine the mechanism responsible for the malfunction of the aqueous outflow pathways in glaucoma. Our hypothesis is that premature or excessive aging changes in the trabecular meshwork, juxtacanalicular tissues, and Schlemm's canal make the aqueous pathways less compliant in OAG. We will test the relationship of aging to the decrease of outflow facility associated with OAG through analysis of electron microscopic findings in normal aging eyes and in glaucomatous eyes. Our hypothesis will be further tested by analysing connective tissue changes in the outflow pathways of steroid-induced glaucoma and the infantile glaucomas associated with mesodermal dysgenesis. Related experimental studies will focus on the effects of elevated intraocular pressure on the outflow pathways and the impact of periorbital and topical corticosteroids on these same tissues.